Camptothecin equilibrium

The lactone form of an analogue of camptothecin converts to its ring-opened carboxylate form. Both forms are in equilibrium. The following degradation data of the lactone form were collected ... 

In contrast to the structurally related topotecan, irinotecan is a prodrug, which has to be converted to its active form, SN-38 (4,30). Cleavage of the side-chain, a bulky piperidino moiety, at the CIO position is rapidly catalysed by carboxylesterases after intravenous administration. SN-38 (7-ethyl-lO-hydroxy-camptothecin) is 1000 times more potent than the parent compound. There is an equilibrium between the active lactone and the inactive carboxylated forms in a pH- and protein-dependent manner for both irinotecan and SN-38 (31,32). 

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